What are typical ivermectin plasma concentration-time profiles for common human dosing regimens?
Executive summary
Typical oral ivermectin in humans reaches peak plasma concentrations roughly 4–10 hours after dosing and has a long elimination phase with half-life estimates ranging from about 18 to as much as 80 hours; a commonly cited Cmax after single oral doses lies in the low‑tens of ng/mL (for example ~20 ng/mL after 0.6 mg/kg and ~40 ng/mL reported after 150 µg/kg in some studies) [1] [2] [3]. Reported profiles show dose‑proportional increases in exposure, substantial between‑subject variability, and food and drug interactions that can shift Cmax and AUC [4] [5] [6].
1. What a “typical” plasma concentration‑time curve looks like
After a single oral dose the plasma concentration rises over several hours to a clear peak and then decays slowly. Multiple sources report tmax (time to Cmax) in the mid‑single‑digit hours — commonly ~4 h but published ranges extend to 10 h — followed by a long terminal phase where mean elimination half‑life estimates vary widely (one review cites ≈25–80 h; some pharmacokinetic reports use ~18 h for particular datasets) [1] [4] [3]. Graphs used in clinical pharmacology papers show a sharp absorption phase to Cmax, then a multi‑day tail compatible with redistribution and slow elimination [7] [4].
2. Typical Cmax and how it scales with dose
Reported Cmax values for human oral dosing are in the low ng/mL range: an oft‑cited figure is ~20 ng/mL after a 0.6 mg/kg single oral dose and other reports reference ~40 ng/mL after a single 150 µg/kg dose in some studies [2] [3]. Trial data indicate plasma exposure increases approximately proportionally with dose across studied ranges (6–120 mg in dose‑escalation work), though absolute Cmax varies by formulation, food state and population [1] [5].
3. Sources of variability you must expect
Large between‑subject differences appear in almost every dataset. A bioequivalence study in Mexico reported average Cmax lower than some previously published populations and emphasised substantial variation among volunteers (n=62) [5]. Food (a high‑fat meal) can raise bioavailability up to ~2.5‑fold versus fasted dosing and co‑administered drugs that affect P‑glycoprotein or CYP enzymes (e.g., ketoconazole, other inhibitors) alter ivermectin plasma exposure in animals and humans [4] [6]. These factors change both Cmax and AUC and explain why single “typical” curves are illustrative rather than definitive [5] [6].
4. Repeated dosing and accumulation
Simulations and animal data show that repeated daily or multiple‑day dosing produces higher troughs and can raise mean 0–24h concentrations compared with a single dose; monkey simulations at 0.3–1.2 mg/kg for seven days illustrate accumulation and higher steady exposure [8]. Human clinical dose‑escalation studies also document proportional increases in systemic exposure with higher or more frequent oral dosing [4] [1]. Exact accumulation in humans depends on interval, dose and individual clearance.
5. Pharmacokinetic parameters that matter clinically
Key parameters reported across studies are tmax ≈4–10 h, Cmax in the low tens of ng/mL for commonly studied oral regimens (examples: ~20 ng/mL after 0.6 mg/kg; ~40 ng/mL after 150 µg/kg in some reports), and a long terminal half‑life spanning ~18 to 80 h in different datasets [1] [2] [3]. Authors modelling tissue exposure (e.g., lung) use plasma profiles from published population PK models to infer tissue partitioning, noting plasma to tissue ratios are model‑dependent [9].
6. Limits of the available reporting and common misinterpretations
Available sources show broad variability and differing study designs; some claims about reaching antiviral in vitro IC50s from single approved oral doses are contradicted by PK simulations showing plasma (and predicted lung) concentrations fall far below in vitro antiviral thresholds — e.g., one analysis concluded approved dosing gives Cmax >35× lower than certain IC50 values [10]. Available sources do not mention a single universal Cmax or half‑life for all humans; they emphasise population‑level ranges and factors that shift exposure [10] [5].
7. Practical takeaway for clinicians and researchers
Expect a rise to peak within hours (typically ≈4 h), low‑ng/mL Cmax at commonly tested single doses, and a long elimination phase with potential for modest accumulation on repeat dosing. Account for food, drug interactions and population differences when interpreting any concentration‑time profile; published simulations and empirical studies provide numeric anchors (Cmax ≈20–40 ng/mL for some regimens; tmax ~4–10 h; t1/2 reported 18–80 h) but individual results will vary [2] [3] [1].
Limitations: this summary uses the sources provided; specific numerical values differ across studies and some datasets are animal or formulation‑specific — where sources do not provide particular human regimens or direct head‑to‑head comparisons, those details are not found in current reporting [8] [11].